Prostaglandin E (PGE) elevates intraocular pressure (IOP) and aqueous humor protein concentration in the rabbit and monkey. Cyclic adenosine monophosphate (c-AMP) is involved in the actions of prostaglandins. Adenylate cyclase, the enzyme which generates c-AMP, and c-AMP phosphodiesterase, the enzyme which inactivates c-AMP, exist in the eye. Ciliary process adenylate cyclase is responsive to PGE. Imidazole is a compound which increases the activity of c-AMP phosphodiesterase in vitro. If the PGE ocular effects are related to increased levels of intraocular c-AMP, agents which stimulate c-AMP phosphodiesterase would antagonize the PG effect. The present proposal is designed to investigate this hypothesis in vivo. The ability of imidazole to inhibit stimuli (PGE, paracentesis, nitrogen mustard, toxic uveitis, arachidonic acid) known to break down the blood aqueous barrier will be determined. Various routes of administration and doses of imidazole will be tested as will congeners of the imidazole compound. The effects of imidazole on aqueous humor concentrations of c-AMP and c-GMP as well as on ciliary body phosphodiesterase activity will be measured. The demonstration of inhibition of in vivo prostaglandin-induced effects by imidazole might provide evidence of c-AMP mediation of these effects and document a new family of potentially useful anti-inflammatory drugs.